Trial Title:
Combining EPI-7386 with Enzalutamide and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer
NCT ID:
NCT06312670
Condition:
Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Prostate Cancer
Prostate Adenocarcinoma
Conditions: Official terms:
Prostatic Neoplasms
Adenocarcinoma
Hypersensitivity
Androgens
Conditions: Keywords:
Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Prostate Cancer
Androgen Deprivation Therapy
Prostate adenocarcinoma
Recurrent metastatic
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Phase 2, single-arm study composed of 2 stages: in the first stage, 13 subjects diagnosed
with mHSPC will be enrolled and treated with EPI-7386 in combination with enzalutamide.
If there are 8 or less subjects with a biochemical response at 6 months, then the trial
will be suspended. Otherwise, 22 additional subjects will be enrolled and treated.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
EPI-7386
Description:
600 mg orally administered twice daily
Arm group label:
EPI-7386 + Enzalutamide
Intervention type:
Drug
Intervention name:
Enzalutamide
Description:
160 mg administered orally once daily, with or without food
Arm group label:
EPI-7386 + Enzalutamide
Intervention type:
Drug
Intervention name:
Androgen Deprivation Therapy (ADT)
Description:
LHRH agonist/antagonist or orchiectomy
Arm group label:
EPI-7386 + Enzalutamide
Summary:
The purpose of this study is to study the effects of EPI-7386 in combination with
Enzalutamide on participants diagnosed with prostate cancer. The main goals of this study
are to evaluate the antitumor activity of EPI-7386 in combination with enzalutamide in
metastatic hormone-sensitive prostate cancer (mHSPC), and to evaluate the
pharmacokinetics (PK) of EPI-7386 when dosed in combination with enzalutamide.
Participants will will take the study drug, EPI-7360, twice a day by mouth and
enzalutamide once a day by mouth, alongside clinic visits every two weeks.
Detailed description:
EPI-7386 is an investigational drug that works by blocking the androgen receptor at a
different site compared to the approved androgen receptor blockers. This may increase the
effectiveness of this drug and increase the effectiveness of approved androgen receptor
blockers when taken together. EPI-7386 is a new drug; therefore, its effectiveness and
safety in prostate cancer patients must be studied before it is approved by the Food and
Drug Administration. EPI-7386 is experimental because it is not currently approved by the
Food and Drug Administration (FDA). Enzalutamide is approved by the FDA for patients
whose prostate cancers has spread after receiving treatment. The hypothesis is that
adding EPI-7386 to standard hormone therapy will be more effective in treating cancer
compared to usual treatment, with the long term goal of discovering more about hormone
therapy as a treatment for cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subjects must have histologically or cytologically confirmed prostate adenocarcinoma
without small cell or neuroendocrine features (please note: >10% small cell or
neuroendocrine differentiation will be excluded).
- Subjects must have received no prior second-generation antiandrogen therapies for
this disease. Androgen deprivation with LHRH agonist/antagonist therapy or history
of bilateral orchiectomy that started less than 12 weeks before study enrollment is
allowed.
- Subjects may have either de novo or recurrent metastatic disease. Presence of
metastatic disease at study entry documented by 1 or more lesions - bone, lymph
node, soft tissue, or visceral metastases - observed by any imaging technique.
- Age >18 years. This study will be limited to adults only.
- Evidence of metastatic disease by conventional CT of chest, abdomen, and pelvis, and
bone scans, OR Positron emission tomography (PET) scan, OR MRI.
- ECOG performance status of 0 to 2.
- Subjects must have normal organ and marrow function as defined below:
- Absolute neutrophil count >1000/μL; platelet count >100 000/μL; hemoglobin >8.5
g/dL) at screening. Note: Subjects must not have received any growth factors
within 7 days or blood transfusions within 14 days prior to the hematologic
laboratory values obtained at screening).
- Total bilirubin (TBIL) <2 × the upper limit of normal (ULN) at screening,
except subjects with documented Gilbert syndrome who must have a TBIL <3 mg/dL
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <5 × ULN at
screening
- Creatinine clearance ≥45 mL/min and/or estimated glomerular filtration rate
(eGFR) ≥30
- Albumin >30 g/L (3.0 g/dL) at screening
- Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g.,
denosumab) must be on a stable dose for at least 28 days before the start of study
treatment.
- Radiation therapy is allowed at any time, as deemed appropriate by the treating
investigator.
- Subjects of child-producing potential agree to use highly effective contraceptive
methods (i.e., barrier contraception measures such as a male condom with spermicide
during intercourse) and avoid sperm donation during the study treatment and for 3
months after the last dose of study treatment. A man is considered to be of
child-producing potential, unless he has had a bilateral vasectomy with documented
aspermia or a bilateral orchiectomy. Partners of participants must also practice
approved forms of birth control.
- Subjects must have the ability to understand and the willingness to sign a written
informed consent form (ICF).
- Members of all races and ethnic groups are eligible for this trial. At least ≥ 20%
of enrolled subjects must be of African American descent. (self-reported).
Exclusion Criteria:
- Evidence of mCRPC.
- Receipt of any other investigational agents.
- Diagnosis of another clinically significant malignancy within the previous 3 years
other than curatively treated non-melanomatous skin cancer or superficial urothelial
carcinoma and other in situ or noninvasive malignancies, as determined by the PI or
CoPI.
- Gastrointestinal issues affecting absorption (e.g., gastrectomy).
- Known history of seizure or conditions that may predispose the subject to seizure,
including brain injury with loss of consciousness, transient ischemic attack within
the past 12 months, cerebral vascular accident, brain metastases, or brain
arteriovenous malformation. Subjects with brain metastases/central nervous system
(CNS) disease that are treated prior to enrollment will be allowed in this clinical
trial.
- Known or suspected hypersensitivity to any components of the formulation used for
EPI-7386 or enzalutamide.
- Use of compounds known to be strong inducers of CYP3A within 30 days prior to start
of study drug treatment, and strong inhibitors of CYP2C8 within 14 days of the first
dose of study treatment.
- Use of narrow therapeutic index sensitive CYP2C8 substrates (e.g., daprobustat,
dasabuvir, repaglinide, paclitaxel) or sensitive substrates for CYP3A.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations considered by the Investigator
to limit compliance with study requirements.
Gender:
Male
Minimum age:
19 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospitals Cleveland Medical Center Seidman Cancer Center, Case Comprehensive Cancer Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Contact:
Last name:
Pedro Barata, MD, MSc
Phone:
216-262-1214
Email:
Pedro.Barata@UHhospitals.org
Facility:
Name:
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Christopher Wee, MD
Phone:
1-866-223 8100
Email:
TaussigResearch@ccf.org
Start date:
May 16, 2024
Completion date:
March 1, 2026
Lead sponsor:
Agency:
Pedro Barata, MD, MSc
Agency class:
Other
Collaborator:
Agency:
ESSA Pharma Inc.
Agency class:
Other
Source:
Case Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06312670
